What the clinician needs to know about chronic renal disease

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Consensus now is that provided non-pregnant renal function is only mildly compromised, proteinuria not in the nephrotic range (3 g/24 h) and hypertension absent or minimal, then obstetric outcome is usually successful with little or no adverse effect on long-term renal prognosis.

Renal dysfunction and the prospects for pregnancy and afterwards

A woman may lose up to 50% of her renal function and still maintain an Scr less than 130 ^mol/l because of hyperfiltration by the remaining nephrons but if renal function is more severely compromised then small further decreases in GFR will cause Scr to increase markedly.

In women with renal disease the pathology may be both biochemically and clinically silent. Most individuals remain symptom-free until their GFR declines to less than 25% of normal, and many serum constituents are frequently normal until a late stage of disease. Degrees of functional impairment that do not cause symptoms or appear to disrupt homoeostasis in non-pregnant individuals can, however, jeopardize pregnancy. Normal pregnancy is rare when renal function declines such that the non-pregnant Scr and Surea exceed 275 ^mol/l and 10 ^mol/l, respectively.

The basic question for a woman with renal disease must be: is pregnancy advisable? If it is, then the sooner she starts to have her family the better, since in many cases renal function will decline with time. Women with suspected or known renal disease, not always counselled prior to pregnancy, may present already pregnant, as a 'fait accompli'; then the question must be: 'does pregnancy continue?'

Obstetric and long-term renal prognoses differ in women with different degrees of renal insufficiency, and the prospects for pregnancy are best considered by categories of functional renal status prior to pregnancy.

Women with normal or only mildly decreased prepreg-nancy renal function (Scr < 125 ^mol/l) usually have a successful obstetric outcome, and pregnancy does not appear to adversely affect the course of their disease. There are exceptions with most strongly advising against pregnancy in women with scleroderma and periarteritis nodosa. A few express reservations when the underlying renal disorder is lupus nephropathy, membranoprolif-erative glomerulonephritis, and perhaps IgA and reflux nephropathies.

Most women will augment GFR, but not as much as in normal pregnant women. Increased proteinuria is common, occurring in 50% of pregnancies (although this is unusual in women with chronic pyelonephritis), and exceeds the nephrotic range (3 g in 24 h) in 50% of women. Perinatal outcome can be jeopardized by uncontrolled hypertension and for some when nephrotic range proteinuria is already present in early pregnancy.

Outlooks are more guarded when renal function is moderately impaired (Scr125--250 ^mol/l) before pregnancy and are very drastically curtailed with severe renal dysfunction (Scr > 250 ^mol/l). Indeed, it is now apparent that once Scr > 125 ^mol/l the next significant cut-offs from the clinical viewpoint are Scr > 180 ^mol/l and >220 ^mol/l (see Table 28.1). These women do, however, become pregnant and their awareness of progress in antenatal care and neonatal provision can encourage them to anticipate good outcomes.

The literature has slowly increased in the last 1015 years and the messages are clear: hypertension is common by term (50%) as is significant proteinuria (40%), as well as deterioration in renal function (at times rapid and substantial) and although the infant survival rates are good (80-90%), rates of premature delivery (60%) and fetal growth restriction (40%) underscore the very high potential for obstetric complications in these women. Not previously realized so clearly were the facts that 30-50% of women with moderate insufficiency experience functional loss more rapidly than would be expected from the natural course of their renal disease, plus poorly controlled hypertension might be a harbinger of poor outcome. As alluded to, once Scr >250 ^mol/l there are big risks of unsuccessful obstetric outcome and accelerated loss of renal function and even terminating the pregnancy may not reverse the decline.

Dialysis has been advocated prophylactically during pregnancy to increase the chances of successful outcome but 'buying time' for fetal maturation in this way is independent of the inexorable declines in renal function ultimately to endstage failure. As extreme prematurity and disturbing, life-threatening maternal problems are commonplace such additional health risks are difficult to justify. Perhaps the aim should be to preserve what little renal function remains and to achieve renal rehabilitation via dialysis and transplantation, after which the question of pregnancy can be considered if appropriate. Some women, however, will be prepared to take a chance and even seek assisted conception in the face of their infertility. As mentioned earlier, this pursuit of pregnancy and the issues surrounding the clinician's obligation to accede to (or refute) care that poses a risk to the woman's health is generating much discussion.

Of utmost importance to all the current controversies is that the literature that forms the basis of our views is primarily retrospective with most patients described having only mild dysfunction and women with severe disease

Table 28.1 Chronic renal disease: functional status, prospects for pregnancy and afterwards

Loss of renal function(%)

Successful

Renal failure

Complicated

obstetric

Persists

within 1 year

Scr (^mol/l)

pregnancy(%)

outcome(%)

In pregnancy post-partum

post-partum(%)

<125

25

98

2 -

-

>125

50

90

40 20

2

>180

90

75

65 40

25

>220

100

60

75 60

40

Scr non-pregnant serum creatinine. Estimates based on literature review (1990-2005) from 217 women in 269 pregnancies that attained at least 24 weeks' gestation.

Scr non-pregnant serum creatinine. Estimates based on literature review (1990-2005) from 217 women in 269 pregnancies that attained at least 24 weeks' gestation.

being limited in number. Confirmation of guidelines, therefore, requires further adequate prospective trials.

Antenatal strategy and decision making

Patients should be seen at 2-week intervals until 32 weeks' gestation, after which assessment should be weekly. Routine serial antenatal observations should be supplemented with

1 assessment of renal function by 24-h creatinine clearance and protein excretion (see Chapter 25);

2 careful blood pressure monitoring for early detection of hypertension and assessment of its severity;

3 early detection of pre-eclampsia;

4 biophysical/ultrasound surveillance of fetal size, development, and well-being;

5 early detection of covert bacteriuria or confirmation of urinary tract infection (UTI).

The crux of management is the balance between maternal prognosis and fetal prognosis - the effect of pregnancy on a particular disease and the effect of that disease on pregnancy. The 'clinical watchpoints' specifically associated with particular renal diseases are summarized in Table 28.2. The following guidelines apply to all clinical situations.

RENAL FUNCTION

If renal function deteriorates significantly at any stage of pregnancy, then reversible causes, such as UTI, subtle dehydration, or electrolyte imbalance (occasionally precipitated by inadvertent diuretic therapy) should be sought. Near term, as in normal pregnancy, a decrease in function of 15-20%, which affects Scr minimally, is permissible. Failure to detect a reversible cause of a significant decrement is grounds to end the pregnancy by elective delivery. When proteinuria occurs and persists, but blood pressure is normal and renal function preserved, pregnancy can be allowed to continue under closer scrutiny.

BLOOD PRESSURE

Blood pressure should be measured in the sitting position with a cuff which is large enough for a particular patient's arm. Phases I and V of the Korotkoff sounds are used. Hypertension is not a disease but one end of a continuous distribution of all individuals' blood pressures. The conventional dividing line for obstetric hypertension is 140/90.

Most of the specific risks of hypertension in pregnancy appear to be related to superimposed pre-eclampsia (see Chapter 25). There is confusion about the true incidence of superimposed pre-eclampsia in women with pre-existing renal disease. This is because the diagnosis cannot be made with certainty on clinical grounds alone; hypertension and proteinuria may be manifestations of the underlying renal disease. Treatment of mild hypertension (diastolic blood pressure less than 95 mmHg in the second trimester or less than 100 mmHg in the third) is not necessary during normal pregnancy, but many would treat women with underlying renal disease more aggressively, believing that this preserves kidney function. Most patients can be taught to take their own blood pressure, but there are still debates about the accuracy of automated devices and the role of ambulatory blood pressure measurements.

FETAL SURVEILLANCE AND TIMING OF DELIVERY

Serial assessment of fetal well-being is essential since renal disease can be associated with fetal growth restriction and, when complications do arise, the judicious moment for intervention can be assessed by fetal status. Current technology should minimize the incidence of intrauterine fetal death as well as neonatal morbidity and mortality. Regardless of gestational age, most babies weighing >1500 g survive better in a special care nursery than in a hostile intrauterine environment. Planned preterm delivery may be necessary if there are signs of impending intrauterine fetal death, if renal function deteriorates substantially, if uncontrollable hypertension supervenes, or if eclampsia

Table 28.2 Chronic renal disease and pregnancy

Renal disease

'Clinical watchpoints'

Chronic glomerulonephritis and focal glomerular sclerosis (FGS)

IgA nephropathy

Chronic pyelonephritis (infectious tubulointerstitial disease) Reflux nephropathy

Urolithiasis

Polycystic kidney disease Diabetic nephropathy

Human immunodeficiency virus with associated nephropathy (HIVAN) Systemic lupus erythematosus

Periarteritis nodosa Scleroderma

Previous urologic surgery

After nephrectomy, solitary and pelvic kidneys

Can be high blood pressure late in pregnancy but usually no adverse effect if renal function is preserved and hypertension absent prepregnancy. Some disagree, believing coagulation changes in pregnancy exacerbate disease, especially immunoglobulin A (IgA) nephropathy, membranoproliferative glomerulonephritis, and FGS Some cite risks of sudden escalating or uncontrolled hypertension and renal deterioration.

Most note good outcome when renal function is preserved Bacteriuria in pregnancy and may lead to exacerbation

Some have emphasized risks of sudden escalating hypertension and worsening of renal function. Consensus now is that results are satisfactory when prepregnancy function is only mildly affected and hypertension is absent. Vigilance for urinary tract infections is necessary Ureteral dilatation and stasis do not seem to affect natural history, but infections can be more frequent. Stents have been successfully placed and sonograpically controlled ureterostomy has been performed during gestation Functional impairment and hypertension are usually minimal in childbearing years No adverse effect on the renal lesion. Increased frequency of infections, oedema or pre-eclampsia. Advanced nephropathy can be a problem Renal component can be nephrotic syndrome or severe impairment. Scanty literature but given ravages of this epidemic then HIVAN should be considered when immuno-compromised proteinuria occurs suddenly, especially in immuno-compromised patients. Prognosis is most favourable if disease is in remission 6 months before conception. Some increase steroid dosage immediately postpartum Fetal prognosis is poor. Maternal death can occur. Therapeutic abortion should be considered If onset during pregnancy, there can be rapid overall deterioration. Reactivation of quiescent scleroderma can occur during pregnancy and post-partum Depending on original reason for surgery, there may be other malformations of the urogenital tract. Urinary tract infection is common during pregnancy and renal function may undergo reversible decrease. No significant obstructive problem, but Caesarean section might be necessary for abnormal presentation or to avoid disruption of the continence mechanism if artificial sphincters or neourethras are present Pregnancy is well tolerated. Might be associated with other malformations of the urogenital tract. Dystocia rarely occurs with a pelvic kidney occurs. Clinicians are still searching for antenatal tests that identify the fetus at risk of intrauterine hypoxia and death. Ideally, such a test should not only be reliable but performed easily and repeatedly.

ROLE OF RENAL BIOPSY IN PREGNANCY

Experience with renal biopsy in pregnancy is sparse, mainly because clinical circumstances rarely justify the risks. Biopsy is therefore usually deferred until after delivery. Reports of excessive bleeding and other complications in pregnant women have led some to consider pregnancy as a relative contraindication to renal biopsy. When renal biopsy is undertaken immediately after delivery in women with well-controlled blood pressure and normal coagulation indices, the morbidity is certainly similar to that reported in non-pregnant patients.

The few generally agreed indications for antepartum biopsy are as follows:

1 Sudden deterioration of renal function before 30 weeks' gestation with no obvious cause. Certain forms of rapidly progressive glomerulonephritis may respond to aggressive treatment with steroid 'pulses', chemotherapy, and/or perhaps plasma exchange, when diagnosed early.

2 Symptomatic nephrotic syndrome before 30 weeks' gestation. While some might consider a therapeutic trial of steroids in such cases, it is best to determine whether the lesion is likely to respond to steroids, because pregnancy is itself a hypercoagulable state prone to deterioration by such treatment. On the other hand, proteinuria alone, in a non-eclamptic pregnant woman with well-preserved renal function and without gross oedema and/or hypoalbuminaemia, suggests the need for close monitoring and deferring biopsy until the puerperium.

3 Presentation with active urinary sediment, proteinuria, and borderline renal function in a woman not evaluated in the past. This is a very controversial area and it could be argued that diagnosis of a collagen disorder such as scleroderma or periarteritis would be grounds for terminating the pregnancy, or that classifying the type of lesion in a woman with lupus could determine the type and intensity of therapy.

SPECIFIC RENAL DISEASES AND PREGNANCY

Table 28.2 lists specific diseases associated with pregnancy, the information having been derived from publications over the past 10-15 years. To recap, the crucial balance between obstetric outcome and long-term renal prognosis depends on prepregnancy renal functional status, the absence or presence of hypertension (and its management) and the renal lesion itself, as well as better fetal surveillance, more timely delivery and ever improving neonatal care.

LONG-TERM EFFECTS OF PREGNANCY IN WOMEN WITH RENAL DISEASE

Pregnancy does not cause deterioration or otherwise affect rate of progression of disease beyond what might be expected in the non-pregnant state, provided prepregnancy kidney dysfunction was minimal or very well controlled and hypertension is absent during pregnancy. An important factor in long-term prognosis could be the sclerotic effect that prolonged gestational renal vasodila-tion might have in the residual (intact) glomeruli of the kidneys of these women. The situation may be worse in a single diseased kidney, where more sclerosis has usually occurred within the fewer (intact) glomeruli. Although the evidence in healthy women and those with mild renal disease argues against hyperfiltration-induced damage in pregnancy, there is little doubt that in some women with moderate dysfunction there can be unpredicted, accelerated, and irreversible renal decline in pregnancy or immediately afterwards (see Table 28.1).

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100 Pregnancy Tips

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